With the exception of the primary visual and auditory cortices, most regions of the cerebral cortex project topographically to the striatum. The corticostriatal projection arises from neurons in layer V of the cortex. Glutamate appears to be the excitatory neurotransmitter of these neurons. The striatum then influences neurons in the nuclei of the thalamus by two pathways: direct and indirect (
Fig.
9.25A ). The thalamic neurons in turn excite neurons of the cerebral cortex thereby forming closed loops with most of the cortex. Several distinct loops have been identified on the basis of cortical regions and function; however, here we will focus on the motor-related loops as a model for basal ganglia operation (
Fig. 9.25A
The overall action of the direct pathway through the basal ganglia to motor areas of the cortex is to enhance motor activity. In the direct pathway, the striatum projects to •Fig. 9.25 Functional Connectivity of the Basal Ganglia for Motor Control. A, Connectionsbetweenvariousbasalgangliacomponentsandotherassociatedmotorareas.TheexcitatorycorticalinputtothecaudateandputameninfluencesoutputfromtheGPiandthesubstantianigraparsreticulata(SNpr)viaadirectandanindirectpathway.Thetwoinhibitorystepsintheindirectpathwaymeanthatactivitythroughthispathwayhasaneffectonbasalgangliaoutputtothethalamusandsuperiorcolliculusoppositethatofthedirectpathway.Dopamine(DA)isaneuromodulatorthatactsonD1andD2receptorsonstriatalneuronsthatparticipateinthedirectandindirectpathways,respectively.B, ChangesinactivityflowthatoccurinParkinson’sdisease,inwhichthesubstantianigraparscompacta(SNpc)degenerates.C, ChangesinactivityflowinHuntington’sdisease,inwhichinhibitorycontroloftheGPeislost.Plus symbols (+)andminus symbols (−),respectively,indicatetheexcitatoryorinhibitorynatureofasynapticconnection.glu,glutamate;GPe,externalglobuspallidus;GPi,internalglobuspallidus;VA/VL,ventralanterior/ventrallateralnucleiofthethalamus.
the internal segment of the globus pallidus (GPi). This projection is inhibitory, and the main transmitter is GABA. The GPi projects to the VA and VL nuclei of the thalamus. These connections also function with GABA and are inhibitory. The VA and VL nuclei send excitatory connections to the prefrontal, premotor, and supplementary motor cortex. This input to the cortex influences motor planning, and it also affects the discharge of corticospinal and corticobulbar neurons.
The direct pathway appears to function as follows: Neurons in the striatum have little background activity, but during movement they are activated by their input from the cortex. In contrast, neurons in the GPi have a high level of background activity. When the striatum is activated, its inhibitory projections to the globus pallidus slow the activity of pallidal neurons. However, the pallidal neurons themselves are inhibitory, and they normally provide tonic inhibition of neurons in the VA and VL nuclei of the thalamus. Therefore, activation of the striatum causes disinhibition of neurons of the VA and VL nuclei. When disinhibited, the VA/VL neurons increase their firing rates, exciting their target neurons in the motor areas of the cerebral cortex. Because the motor areas evoke movement by activating α and γ motor neurons in the spinal cord and brainstem, the basal ganglia can regulate movement by enhancing the activity of neurons in the motor cortex.